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RNAcontacts: A Pipeline for Predicting Contacts from RNA Proximity Ligation Assays. RNA接触:从RNA邻近连接分析预测接触的管道。
IF 2 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2023-01-01 DOI: 10.32607/actanaturae.11893
S D Margasyuk, M A Vlasenok, G Li, Ch Cao, D D Pervouchine

High-throughput RNA proximity ligation assays are molecular methods that are used to simultaneously analyze the spatial proximity of many RNAs in living cells. Their principle is based on cross-linking, fragmentation, and subsequent religation of RNAs, followed by high-throughput sequencing. The generated fragments have two different types of splits, one resulting from pre-mRNA splicing and the other formed by the ligation of spatially close RNA strands. Here, we present RNAcontacts, a universal pipeline for detecting RNA-RNA contacts in high-throughput RNA proximity ligation assays. RNAcontacts circumvents the inherent problem of mapping sequences with two distinct types of splits using a two-pass alignment, in which splice junctions are inferred from a control RNA-seq experiment on the first pass and then provided to the aligner as bona fide introns on the second pass. Compared to previously developed methods, our approach allows for a more sensitive detection of RNA contacts and has a higher specificity with respect to splice junctions that are present in the biological sample. RNAcontacts automatically extracts contacts, clusters their ligation points, computes the read support, and generates tracks for visualizing through the UCSC Genome Browser. The pipeline is implemented in Snakemake, a reproducible and scalable workflow management system for rapid and uniform processing of multiple datasets. RNAcontacts is a generic pipeline for the detection of RNA contacts that can be used with any proximity ligation method as long as one of the interacting partners is RNA. RNAcontacts is available via the GitHub repository https://github.com/smargasyuk/ RNAcontacts/.

高通量RNA邻近连接分析是用于同时分析活细胞中许多RNA的空间邻近性的分子方法。它们的原理是基于RNA的交联、断裂和随后的再结合,然后是高通量测序。产生的片段有两种不同类型的分裂,一种是由前信使核糖核酸剪接产生的,另一种是通过连接空间紧密的核糖核酸链形成的。在这里,我们介绍了RNAcontacts,这是一种在高通量RNA邻近连接分析中检测RNA-RNA接触的通用管道。RNAcontacts绕过了使用双通路比对用两种不同类型的分裂绘制序列的固有问题,在双通路比对中,剪接连接是从第一通路的对照RNA-seq实验中推断出来的,然后在第二通路中作为真正的内含子提供给比对器。与以前开发的方法相比,我们的方法允许对RNA接触进行更灵敏的检测,并且对于生物样品中存在的剪接连接具有更高的特异性。RNAcontacts自动提取联系人,对其连接点进行聚类,计算读取支持,并通过UCSC基因组浏览器生成可视化轨迹。该管道在Snakemake中实现,这是一个可复制和可扩展的工作流管理系统,用于快速、统一地处理多个数据集。RNAcontacts是一种用于检测RNA接触的通用管道,只要相互作用的伴侣之一是RNA,就可以与任何邻近连接方法一起使用。RNAcontacts可通过GitHub存储库获得https://github.com/smargasyuk/RNA联系人/。
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引用次数: 0
Specificity of Penicillin Acylases in Deprotection of N-Benzyloxycarbonyl Derivatives of Amino Acids. 青霉素酰化酶在氨基酸N-苄氧羰基衍生物脱保护中的特异性。
IF 2 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2023-01-01 DOI: 10.32607/actanaturae.13703
I A Morozova, D T Guranda, N V Panin, V K Švedas

Changes in the structure of the N-acyl group in N-acylated amino acid derivatives significantly affect both the recognition and activity of penicillin acylases on this series of substrates. However, penicillin acylases from both Alcaligenes faecalis and Escherichia coli are capable of removing the N-benzyloxycarbonyl protecting group in amino acid derivatives under mild conditions without the use of toxic reagents. Efficiency in using penicillin acylases in preparative organic synthesis can be improved by utilizing modern rational enzyme design methods.

N-酰基化氨基酸衍生物中N-酰基结构的变化显著影响青霉素酰化酶在该系列底物上的识别和活性。然而,来自粪产碱杆菌和大肠杆菌的青霉素酰化酶能够在温和条件下去除氨基酸衍生物中的N-苄氧羰基保护基,而不使用有毒试剂。利用现代合理的酶设计方法可以提高青霉素酰化酶在制备性有机合成中的应用效率。
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引用次数: 0
Creation of Recombinant Biocontrol Agents by Genetic Programming of Yeast. 酵母基因程序设计构建重组生物防治剂。
IF 2 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2023-01-01 DOI: 10.32607/actanaturae.11878
S O Pipiya, N Z Mirzoeva, M N Baranova, I E Eliseev, Yu A Mokrushina, O V Shamova, A G Gabibov, I V Smirnov, S S Terekhov

Bacterial infections caused by antibiotic-resistant pathogens pose an extremely serious and elusive problem in healthcare. The discovery and targeted creation of new antibiotics are today among the most important public health issues. Antibiotics based on antimicrobial peptides (AMPs) are of particular interest due to their genetically encoded nature. A distinct advantage of most AMPs is their direct mechanism of action that is mediated by their membranolytic properties. The low rate of emergence of antibiotic resistance associated with the killing mechanism of action of AMPs attracts heightened attention to this field. Recombinant technologies enable the creation of genetically programmable AMP producers for large-scale generation of recombinant AMPs (rAMPs) or the creation of rAMP-producing biocontrol agents. The methylotrophic yeast Pichia pastoris was genetically modified for the secreted production of rAMP. Constitutive expression of the sequence encoding the mature AMP protegrin-1 provided the yeast strain that effectively inhibits the growth of target gram-positive and gram-negative bacteria. An antimicrobial effect was also observed in the microculture when a yeast rAMP producer and a reporter bacterium were co-encapsulated in droplets of microfluidic double emulsion. The heterologous production of rAMPs opens up new avenues for creating effective biocontrol agents and screening antimicrobial activity using ultrahigh-throughput technologies.

由抗生素耐药性病原体引起的细菌感染在医疗保健中构成了一个极其严重和难以捉摸的问题。新抗生素的发现和有针对性的创造是当今最重要的公共卫生问题之一。基于抗菌肽(AMPs)的抗生素由于其基因编码的性质而引起特别的兴趣。大多数AMPs的一个明显优势是它们的直接作用机制,由它们的膜溶解特性介导。与AMPs的杀伤机制相关的抗生素耐药性的低出现率引起了该领域的高度关注。重组技术能够创建基因可编程的AMP生产商,用于大规模生产重组AMP(rAMP)或创建生产rAMP的生物控制剂。对甲基营养酵母毕赤酵母进行基因改造,用于分泌rAMP。编码成熟AMP蛋白-1的序列的组成型表达提供了有效抑制目标革兰氏阳性菌和革兰氏阴性菌生长的酵母菌株。当酵母rAMP生产者和报告菌共同包封在微流体双乳液的液滴中时,在微培养中也观察到了抗菌效果。rAMP的异源生产为创造有效的生物控制剂和使用超高通量技术筛选抗菌活性开辟了新的途径。
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引用次数: 0
Biomedical Nanosystems for In Vivo Detoxification: From Passive Delivery Systems to Functional Nanodevices and Nanorobots. 用于体内排毒的生物医学纳米系统:从被动给药系统到功能纳米设备和纳米机器人。
IF 2 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.32607/actanaturae.15681
T N Pashirova, Z M Shaihutdinova, V F Mironov, P Masson

The problem of low efficiency of nanotherapeutic drugs challenges the creation of new alternative biomedical nanosystems known as robotic nanodevices. In addition to encapsulating properties, nanodevices can perform different biomedical functions, such as precision surgery, in vivo detection and imaging, biosensing, targeted delivery, and, more recently, detoxification of endogenous and xenobiotic compounds. Nanodevices for detoxification are aimed at removing toxic molecules from biological tissues, using a chemical- and/or enzyme-containing nanocarrier for the toxicant to diffuse inside the nanobody. This strategy is opposite to drug delivery systems that focus on encapsulating drugs and releasing them under the influence of external factors. The review describes various kinds of nanodevices intended for detoxification that differ by the type of poisoning treatment they provide, as well as the type of materials and toxicants. The final part of the review is devoted to enzyme nanosystems, an emerging area of research that provides fast and effective neutralization of toxins in vivo.

纳米治疗药物效率低的问题挑战了被称为机器人纳米设备的新的替代生物医学纳米系统的创建。除了封装特性外,纳米器件还可以执行不同的生物医学功能,如精确手术、体内检测和成像、生物传感、靶向递送,以及最近对内源性和外源性化合物的解毒。用于解毒的纳米设备旨在从生物组织中去除有毒分子,使用含有化学物质和/或酶的纳米载体使毒物在纳米体内扩散。这种策略与专注于封装药物并在外部因素影响下释放药物的药物递送系统相反。这篇综述描述了各种用于解毒的纳米设备,它们提供的中毒治疗类型以及材料和毒物的类型不同。综述的最后一部分致力于酶纳米系统,这是一个新兴的研究领域,可以在体内快速有效地中和毒素。
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引用次数: 1
An Analysis of Genetic Predisposition to Hereditary Catalepsy in a Mouse Model of Neuropsychiatric Disorders Using Whole-Genome Sequencing Data. 使用全基因组测序数据分析神经精神疾病小鼠模型中遗传性癫痫的遗传倾向。
IF 2 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.32607/actanaturae.11875
T V Andreeva, F E Gusev, N A Sinyakova, A V Kulikov, A P Grigorenko, I Yu Adrianova, D V Bazovkina, E I Rogaev

Catalepsy is a behavioral condition that is associated with severe psychopathologies, including schizophrenia, depression, and Parkinson's disease. In some mouse strains, catalepsy can be induced by pinching the skin at the scruff of the neck. The main locus of hereditary catalepsy in mice has recently been linked to the 105-115 Mb fragment of mouse chromosome 13 by QTL analysis. We performed whole-genome sequencing of catalepsy-resistant and catalepsy-prone mouse strains in order to pinpoint the putative candidate genes related to hereditary catalepsy in mice. We remapped the previously described main locus for hereditary catalepsy in mice to the chromosome region 103.92-106.16 Mb. A homologous human region on chromosome 5 includes genetic and epigenetic variants associated with schizophrenia. Furthermore, we identified a missense variant in catalepsy-prone strains within the Nln gene. Nln encodes neurolysin, which degrades neurotensin, a peptide reported to induce catalepsy in mice. Our data suggest that Nln is the most probable candidate for the role of major gene of hereditary, pinch-induced catalepsy in mice and point to a shared molecular pathway between catalepsy in mice and human neuropsychiatric disorders.

Catalepsy是一种与严重精神病理学相关的行为状况,包括精神分裂症、抑郁症和帕金森病。在一些小鼠品系中,可以通过捏脖子后面的皮肤来诱导催化作用。最近通过QTL分析将小鼠遗传性催化的主要基因座与小鼠13号染色体的105-115Mb片段连接。我们对耐催化和易催化的小鼠菌株进行了全基因组测序,以确定与小鼠遗传性催化相关的假定候选基因。我们将先前描述的小鼠遗传性催化的主要基因座重新映射到染色体区域103.922-16.16Mb。5号染色体上的同源人类区域包括与精神分裂症相关的遗传和表观遗传变异。此外,我们在Nln基因内的易催化菌株中发现了一种错义变体。Nln编码神经溶素,它降解神经降压素,一种据报道在小鼠中诱导催化的肽。我们的数据表明,Nln是遗传性、夹激诱导的小鼠催化主要基因作用的最有可能的候选者,并指出小鼠催化和人类神经精神疾病之间存在共同的分子途径。
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引用次数: 0
Genetic Variants Associated with Bronchial Asthma Specific to the Population of the Russian Federation. 俄罗斯联邦人群特有的与支气管哮喘相关的遗传变异。
IF 2 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2023-01-01 DOI: 10.32607/actanaturae.11853
Y N Akhmerova, T A Shpakova, K S Grammatikati, S I Mitrofanov, P G Kazakova, A A Mkrtchian, P U Zemsky, M N Pilipenko, N V Feliz, L V Frolova, A A Frolovskaya, V S Yudin, A A Keskinov, S A Kraevoy, S M Yudin, V I Skvortsova

Bronchial asthma (BA) is a disease that still lacks an exhaustive treatment protocol. In this regard, the global medical community pays special attention to the genetic prerequisites for the occurrence of this disease. Therefore, the search for the genetic polymorphisms underlying bronchial asthma has expanded considerably. As the present study progressed, a significant amount of scientific medical literature was analyzed and 167 genes reported to be associated with the development of bronchial asthma were identified. A group of participants (n = 7,303) who had voluntarily provided their biomaterial (venous blood) to be used in the research conducted by the Federal Medical Biological Agency of Russia was formed to subsequently perform a bioinformatic verification of known associations and search for new ones. This group of participants was divided into four cohorts, including two sex-distinct cohorts of individuals with a history of asthma and two sex-distinct cohorts of apparently healthy individuals. A search for polymorphisms was made in each cohort among the selected genes, and genetic variants were identified whose difference in occurrence in the different cohorts was statistically significant (significance level less than 0.0001). The study revealed 11 polymorphisms that affect the development of asthma: four genetic variants (rs869106717, rs1461555098, rs189649077, and rs1199362453), which are more common in men with bronchial asthma compared to apparently healthy men; five genetic variants (rs1923038536, rs181066119, rs143247175, rs140597386, and rs762042586), which are more common in women with bronchial asthma compared to apparently healthy women; and two genetic variants (rs1219244986 and rs2291651) that are rare in women with a history of asthma.

支气管哮喘(BA)是一种仍然缺乏详尽治疗方案的疾病。在这方面,全球医学界特别关注这种疾病发生的遗传先决条件。因此,对支气管哮喘遗传多态性的研究已经大大扩展。随着本研究的进展,分析了大量的科学医学文献,并鉴定了167个与支气管哮喘发展相关的基因。一组参与者(n=7303)自愿提供了他们的生物材料(静脉血),用于俄罗斯联邦医学生物局进行的研究,随后对已知的关联进行了生物信息学验证,并寻找新的关联。这组参与者被分为四个队列,包括有哮喘病史的两个性别不同的队列和明显健康的两个不同性别的队列。在所选基因中的每个队列中搜索多态性,并确定了遗传变异,其在不同队列中的发生差异具有统计学意义(显著性水平低于0.0001)。该研究揭示了11种影响哮喘发展的多态性:四种遗传变异(rs869106717、rs1461555098、rs189649077和rs1199362453),与明显健康的男性相比,其在患有支气管哮喘的男性中更常见;五种遗传变异(rs1923038536、rs181066119、rs143247175、rs140597386和rs762042586),与明显健康的女性相比,在患有支气管哮喘的女性中更常见;以及两种在有哮喘病史的女性中罕见的遗传变异(rs1219244986和rs2291651)。
{"title":"Genetic Variants Associated with Bronchial Asthma Specific to the Population of the Russian Federation.","authors":"Y N Akhmerova, T A Shpakova, K S Grammatikati, S I Mitrofanov, P G Kazakova, A A Mkrtchian, P U Zemsky, M N Pilipenko, N V Feliz, L V Frolova, A A Frolovskaya, V S Yudin, A A Keskinov, S A Kraevoy, S M Yudin, V I Skvortsova","doi":"10.32607/actanaturae.11853","DOIUrl":"10.32607/actanaturae.11853","url":null,"abstract":"<p><p>Bronchial asthma (BA) is a disease that still lacks an exhaustive treatment protocol. In this regard, the global medical community pays special attention to the genetic prerequisites for the occurrence of this disease. Therefore, the search for the genetic polymorphisms underlying bronchial asthma has expanded considerably. As the present study progressed, a significant amount of scientific medical literature was analyzed and 167 genes reported to be associated with the development of bronchial asthma were identified. A group of participants (n = 7,303) who had voluntarily provided their biomaterial (venous blood) to be used in the research conducted by the Federal Medical Biological Agency of Russia was formed to subsequently perform a bioinformatic verification of known associations and search for new ones. This group of participants was divided into four cohorts, including two sex-distinct cohorts of individuals with a history of asthma and two sex-distinct cohorts of apparently healthy individuals. A search for polymorphisms was made in each cohort among the selected genes, and genetic variants were identified whose difference in occurrence in the different cohorts was statistically significant (significance level less than 0.0001). The study revealed 11 polymorphisms that affect the development of asthma: four genetic variants (rs869106717, rs1461555098, rs189649077, and rs1199362453), which are more common in men with bronchial asthma compared to apparently healthy men; five genetic variants (rs1923038536, rs181066119, rs143247175, rs140597386, and rs762042586), which are more common in women with bronchial asthma compared to apparently healthy women; and two genetic variants (rs1219244986 and rs2291651) that are rare in women with a history of asthma.</p>","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9431717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
B Cell Profiling in Patients with Pemphigus Vulgaris. 寻常型天疱疮患者的B细胞图谱。
IF 2 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.32607/actanaturae.11890
V A Abrikosova, Y A Mokrushina, L A Ovchinnikova, E N Larina, S S Terekhov, M N Baranova, Y A Lomakin, D S Balabashin, T V Bobik, E N Kaliberda, V D Knorre, M V Shpilevaya, T K Aliev, D G Deryabin, A E Karamova, A A Kubanov, M P Kirpichnikov, I V Smirnov

Pemphigus vulgaris is a severe, socially significant autoimmune disease associated with autoantibodies to the desmoglein 3 antigen. The disease affects all age groups, beginning at 18 years of age; the mortality rate of pemphigus can reach as high as 50%, depending on a patient's age and a number of other factors. There is no highly selective or personalized therapy for pemphigus vulgaris at the moment. One of the well-known therapeutic approaches to the disease is to use rituximab, an anti-CD20 antibody that can help achieve B cell depletion in peripheral blood. To solve the problem of nonspecific elimination of B cells in patients with pemphigus vulgaris, it is reasonable to use specific immunoligands, their choice being based on an assessment of the level of autoantibodies specific to each of the fragments of desmoglein. In this work, the proportion of autoreactive B cells in patients diagnosed with pemphigus vulgaris is found to be 0.09-0.16%; a positive correlation was revealed between the antibody level and the number of autoreactive B cells to various fragments of desmoglein.

寻常性天疱疮是一种严重的、具有社会意义的自身免疫性疾病,与桥粒蛋白3抗原自身抗体相关。这种疾病影响所有年龄组,从18岁开始;天疱疮的死亡率可能高达50%,这取决于患者的年龄和许多其他因素。目前还没有高度选择性或个性化的治疗寻常型天疱疮的方法。众所周知的治疗方法之一是使用利妥昔单抗,这是一种抗CD20抗体,可以帮助实现外周血中B细胞的耗竭。为了解决寻常型天疱疮患者B细胞非特异性消除的问题,使用特异性免疫配体是合理的,它们的选择是基于对每个链蛋白片段特异性自身抗体水平的评估。在这项工作中,发现诊断为寻常型天疱疮的患者中自身反应性B细胞的比例为0.09-0.16%;抗体水平与对各种链蛋白片段的自身反应性B细胞的数量之间显示出正相关。
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引用次数: 0
Distortion of Population Statistics due to the Use of Different Methodological Approaches to the Construction of Genomic DNA Libraries. 由于使用不同的方法构建基因组DNA文库而导致的人口统计失真。
IF 2 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.32607/actanaturae.11898
F S Sharko, K V Zhur, V A Trifonov, E B Prokhortchouk

Several different methods of DNA library preparation for paleogenetic studies are now available. However, the chemical reactions underlying each of them can affect the primary sequence of ancient DNA (aDNA) in the libraries and taint the results of a statistical analysis. In this paper, we compare the results of a sequencing of the aDNA libraries of a Bronze Age sample from burials of the Caucasian burial ground Klady, prepared using three different approaches: (1) shotgun sequencing, (2) strategies for selecting target genomic regions, and (3) strategies for selecting target genomic regions, including DNA pre-treatment with a mixture of uracil-DNA glycosylase (UDG) and endonuclease VIII. The impact of the studied approaches to genomic library preparation on the results of a secondary analysis of the statistical data, namely F4 statistics, ADMIXTURE, and principal component analysis (PCA), was analyzed. It was shown that preparation of genomic libraries without the use of UDG can result in distorted statistical data due to postmortem chemical modifications of the aDNA. This distortion can be alleviated by analyzing only the single nucleotide polymorphisms caused by transversions in the genome.

用于古遗传学研究的几种不同的DNA文库制备方法现在可用。然而,它们背后的化学反应可能会影响文库中古代DNA(aDNA)的一级序列,并影响统计分析的结果。在本文中,我们比较了使用三种不同方法制备的高加索墓地克拉迪青铜时代样本的aDNA文库的测序结果:(1)鸟枪测序,(2)选择目标基因组区域的策略,和(3)选择目标基因区域的策略,包括用尿嘧啶DNA糖苷酶(UDG)和核酸内切酶VIII的混合物进行DNA预处理。分析了所研究的基因组文库制备方法对统计数据二次分析结果的影响,即F4统计、ADMIXTURE和主成分分析(PCA)。研究表明,由于aDNA的死后化学修饰,在不使用UDG的情况下制备基因组文库可能导致统计数据失真。这种扭曲可以通过只分析基因组中由颠换引起的单核苷酸多态性来减轻。
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引用次数: 1
Evaluation of the Effectiveness of Various Autophagy Inhibitors in A549 Cancer Stem Cells. 各种自噬抑制剂对A549癌症干细胞的有效性评价。
IF 2 4区 生物学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-01-01 DOI: 10.32607/actanaturae.11891
K V Aleksandrova, I I Suvorova

Numerous studies have already established that autophagy plays a central role in the survival of all cells, including malignant ones. Autophagy is a central cog in the general mechanism that provides the intracellular proteostasis determining cellular physiological and phenotypic characteristics. The accumulated data show that autophagy largely contributes to cancer cell stemness. Thus, autophagy modulation is considered one of the promising pharmacological targets in therapy aimed at cancer stem cell elimination. However, autophagy is a multi-stage intracellular process that involves numerous protein participants. In addition, the process can be activated simultaneously by various signaling modules. Therefore, it is no small feat to select an effective pharmacological drug against autophagy. What's more, the search for potential chemotherapeutic agents that could eliminate cancer stem cells through pharmacological inhibition of autophagy is still under way. In the present work, we selected a panel of autophagy inhibitors (Autophinib, SBI-0206965, Siramesine, MRT68921, and IITZ-01), some of whom have been recently identified as effective autophagy inhibitors in cancer cells. Using A549 cancer cells, which express the core stem factors Oct4 and Sox2, we evaluated the effect of these drugs on the survival and preservation of the original properties of cancer stem cells. Among the agents selected, only Autophinib demonstrated a significant toxic effect on cancer stem cells. The obtained results demonstrate that autophagy inhibition by Autophinib downregulates the expression of the Sox2 protein in A549 cells, and that this downregulation correlates with a pronounced induction of apoptosis. Moreover, Autophinib-treated A549 cells are unable to form spheroids, which indicates a reduction in stemness. Thus, among the drugs studied, only Autophinib can be considered a potential agent against cancer stem cells.

许多研究已经证实,自噬在包括恶性细胞在内的所有细胞的生存中起着核心作用。自噬是提供决定细胞生理和表型特征的细胞内蛋白稳定的一般机制中的一个核心环节。积累的数据表明,自噬在很大程度上促成了癌症细胞的干燥。因此,在旨在消除癌症干细胞的治疗中,自噬调节被认为是有前景的药理靶点之一。然而,自噬是一个多阶段的细胞内过程,涉及许多蛋白质参与者。此外,该过程可以由各种信令模块同时激活。因此,选择一种有效的抗自噬药物绝非易事。更重要的是,寻找可以通过药物抑制自噬来消除癌症干细胞的潜在化学治疗剂的工作仍在进行中。在目前的工作中,我们选择了一组自噬抑制剂(Autophinib、SBI-0206965、Siramesine、MRT68921和IITZ-01),其中一些最近被鉴定为癌症细胞中有效的自噬抑制剂。使用表达核心干细胞因子Oct4和Sox2的A549癌症细胞,我们评估了这些药物对癌症干细胞存活和原始特性保存的影响。在选择的药物中,只有Autophinib对癌症干细胞具有显著的毒性作用。所获得的结果表明,Autophinib的自噬抑制下调A549细胞中Sox2蛋白的表达,并且这种下调与细胞凋亡的显著诱导相关。此外,Autophinib处理的A549细胞不能形成球体,这表明干性降低。因此,在所研究的药物中,只有Autophinib可以被认为是对抗癌症干细胞的潜在药物。
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引用次数: 0
The Relationship of Precursor Cluster Concentration in a Saturated Crystallization Solution to Long-Range Order During the Transition to the Solid Phase. 饱和结晶溶液中前体团簇浓度与向固相过渡过程中长程有序度的关系。
IF 2 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2023-01-01 DOI: 10.32607/actanaturae.11815
M A Marchenkova, A S Boikova, K B Ilina, P V Konarev, Yu V Pisarevsky, Yu A Dyakova, M V Kovalchuk

A model for the transition from disordered liquid state to the solid phase has been proposed based on establishing a correlation between the concentration of precursor clusters in a saturated solution and the features of solid phase formation. The validity of the model has been verified experimentally by simultaneously studying the oligomeric structure of lysozyme protein solutions and the peculiarities of solid phase formation from these solutions. It was shown that no solid phase is formed in the absence of precursor clusters (octamers) in solution; perfect monocrystals are formed at a small concentration of octamers; mass crystallization is observed with an increasing degree of supersaturation (and concentration of octamers); further increase in octamer concentration leads to the formation of an amorphous phase.

在建立饱和溶液中前体团簇浓度与固相形成特征之间的相关性的基础上,提出了一种从无序液态向固相过渡的模型。通过同时研究溶菌酶蛋白溶液的低聚结构和这些溶液形成固相的特性,实验验证了该模型的有效性。研究表明,在溶液中不存在前体簇(八聚体)的情况下,不会形成固相;在小浓度的八聚体下形成完美的单晶;随着过饱和度(和八聚体浓度)的增加,观察到质量结晶;八聚体浓度的进一步增加导致无定形相的形成。
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